265114-54-3
基本信息
化合物 T28942
SOT 095
telomestatin
(R)-Telomestatin
YVSQVYZBDXIXCC-INIZCTEOSA-N
3,7,11,15,19,23,27-Heptaoxa-31-thia-33,34,35,36,37,38,39,40-octaazanonacyclo[28.2.1.12,5.16,9.110,13.114,17.118,21.122,25.126,29]tetraconta-2(40),4,6(39),8,10(38),12,14(37),16,18(36),20,22(35),24,26(34),28,30(33)-pentadecaene, 4,8-dimethyl-, (1R)-
常見問題列表
Traditional Cytotoxic Agents
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Telomestatin (0-50 μM) promotes or stabilizes the formation of the intramolecular G-quadruplex. At the DNA concentrations of 0.005 and 0.2 μM, EC 50 values of 0.03 μM and 0.53 μM telomestatin are found. In a parallel experiment with the mutated oligonucleotide d[T2AGAG]4, there is no conversion of the mutated sequence to a G-quadruplex structure by telomestatin.Telomestatin (2-10?μM) effects the expression of DN-hTERT on telomerase activity and telomere length, at 10?μM,the expression of DN-hTERT shows a significant reduction of telomerase activity. Additionally, at 2?μM?, the terminal restriction fragment (TRF) length of U937 cells shortens progressively from 9.5 to 3.8?kb at population doubling (PD) 20 in U937 cells.Telomestatin (2-5?μM; short-time or long trem) has less effect on normal diploid human fibroblasts and ALT-positive cells.Telomestatin (5?μM; short-time 3 days) exposure has no affect the viability of normal human fibroblasts BJ or IMR-90; however, 5?μM?of telomestatin reduces the viability of GM847 cells.Telomestatin (2 μM; long-term 10-50 days) does not significantly change the proliferation rate or viability to that of control cells in BJ or IMR-90 cells and also does not change the proliferation of GM847 cells.
Telomestatin (intraperitoneal injection; 3-15 mg/kg; two times a week; 4 weeks) decreases tumor telomerase activity and inhibits the growth of U937 xenografts. Systemic administrations of 3?mg/kg or 9?mg/kg or 15?mg/kg of telomestatin decreases tumor telomerase activity by 60.2%, 74% and 92.5% compared to control, respectively.
Animal Model: | Mice model with U937 xenografts |
Dosage: | 3-15 mg/kg |
Administration: | Intraperitoneal injection; 3-15 mg/kg; two times a week; 4 weeks |
Result: | Treated with PBS for 21 days had a mean tumor volume of 1395?mm 3 compared with telomestatin treated with a mean tumor volume of 291?mm 3 .Exhibited no adverse effects (body weight loss, clinical signs or survival).Reduced U937 cells in bone marrow and recovered the normal hematopoiesis in mice. |